An Investigation of Early Life Stress and Depression

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Severe childhood adversity, including childhood sexual abuse (CSA), explains 32-44% of psychiatric disorders and is associated with substantially increased risks for depression and substance abuse later in life. However, 20-40% of adults with a history of CSA report little to no consequences. The neurobiological underpinnings associated with adaptive (resilience) and maladaptive consequences of CSA remain largely unknown. The goal of this study is to investigate brain pathways within adult females (with a history of CSA that occurred between the ages of 5-9) with and without a current diagnosis of major depressive disorder (MDD). We hypothesize that the CSA/MDD participants will be characterized by (1) reduced reward responsiveness and prefrontal cortex activity, but increased cortisol levels, (2) reduced dopamine activity, and (3) reduced dopamine transporter binding. The over-arching purpose of the study is to (1) identify individuals at risk for psychopathology and maladaptive behavior, (2) prevent re-victimization, and (3) develop more targeted therapeutic interventions.

This study involves 4 sessions, described below.

Session 1 (SCID Session) The first session takes place at the Center for Depression, Anxiety, and Stress Research (CDASR) or Neuroimaging Center (both at McLean Hospital) and involves consenting, a clinical evaluation, a series of questionnaires, and a medical assessment.

Session 2 or 3 (fMRI Session) The third session takes place at the Neuroimaging Center. Using a double-blind design, participants will be administered either amisulpride (50 mg) or placebo. Participants will complete the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging (fMRI) and the Probabilistic Stimulus Selection Task (PSST) afterwards.

Session 2 or 3 (PET Session) This session takes place at Massachusetts General Hospital. 9 mCi of [11C] altropane will be injected by a trained nuclear medicine technician and positron emission tomography (PET) scanning will begin. Prior to the PET scan, a blood serum pregnancy test will be administered for females.

Participants are exposed to stress, in the form of negative performance feedback, during session 2. Saliva is collected before and following stress exposure. Cortisol levels are measured giving a correlate of stress response.

Brain activity and structure is measured using various MRI techniques, including fMRI, DTI, and structural scans. Participants perform the Monetary Incentive Delay (MID) task during the fMRI. Resting-state fMRI data are also collected.

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Ages Eligible for Study:

20 Years to 45 Years (Adult)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

General Inclusion Criteria:

Females of all ethnic origins, age between 20 and 45; right-handed (Chapman & Chapman 1987);

Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine; 6 months for neuroleptics; 2 weeks for benzodiazepines; 2 weeks for any other antidepressants);

Inclusion Criteria for Childhood Sexual Abuse/MDD (CSA/MDD) Group:

At least one incident of contact sexual abuse1 between the ages 5-14 years;

Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of the SCID);